HUMULIN

Serious Warnings and Precautions Hypoglycemia (too little sugar in the blood) is the most common adverse effect of insulin products. Glucose monitoring should be performed for all patients with diabetes mellitus treated with insulins.

Uncorrected hypoglycemic or hyperglycemic reactions can cause loss of consciousness, coma or even death. A few patients who experienced hypoglycemic reactions after being transferred to HUMULIN (insulin, human biosynthetic) have reported that these early warning symptoms were less pronounced than they were with animal-source insulin.

Any change of insulin regimen should be made cautiously and only under medical supervision. Fast-acting insulins should be combined with a longer- acting insulin or insulin infusion pump therapy to maintain adequate glucose control.

HUMULIN R should not be mixed with any other insulin unless clearly indicated and done under medical supervision. The contents of the cartridge of HUMULIN R should be clear. Do not use if cloudy.  Each case of diabetes is different. Your doctor has told you which insulin to use, how much, and when and how often to inject it.

This schedule has been individualized for you. Proper control of your diabetes requires close and constant cooperation with your doctor.  You have been instructed to test your blood and/or your urine regularly for sugar. If your blood tests consistently show above or below normal sugar levels or your urine tests consistently show the presence of sugar, your diabetes is not properly controlled and you must let your doctor know.

 If you become ill from any cause, especially with nausea and vomiting, your insulin requirements may change. Test your blood and/or urine and notify your doctor at once.  Always keep an extra supply of insulin. Always wear diabetic identification so that appropriate treatment can be given if complications occur away from home.

 Never change from the insulin that has been prescribed for you to another insulin without instructions from your doctor. Changing the type, strength, source, or manufacturer of insulin can cause problems with your blood sugar control.

 Some patients taking HUMULIN R will require a change in dosage from that used with animal-source insulins. If an adjustment is needed, it may be made with the first dose or over a period of several weeks.  Take precautions to avoid hypoglycemia while driving or operating machinery.

This is particularly important in patients who have reduced awareness of the warning signs of hypoglycemia or who have frequent episodes of hypoglycemia.  Ability to concentrate and react may be impaired as a result of hyperglycemia or as a result of hyperglycemia- induced visual impairment.

Take caution in situations that require these abilities such as driving or operating machinery.  Your doctor will tell you what to do if you miss a dose of insulin or miss a meal because of illness. If you miss a meal, as a substitute use sugar, sugar-sweetened candy, fruit juice, or sugar-sweetened beverage according to your doctor's instructions.

If a shortage of insulin appears inevitable, a temporary reduction in the size of dose may be made, accompanied by limitation of food to two-thirds its usual quantity and a liberal increase in fluids of little or no food value, such as water, tea, coffee, broths, or clear soups.

 Consult your doctor if you notice anything unusual or have doubts about your condition or your use of insulin.  Consult your doctor concerning adjustments in your insulin schedule if you travel across more than 2 time zones. INTERACTIONS WITH THIS MEDICATION There may be interactions between HUMULIN R and other medicines.

Tell your doctor if you are taking any other medicine which has been prescribed for you or which you bought without a prescription. Insulin requirements may be increased if you are taking other drugs with hyperglycemic activity, such as oral contraceptives (for example, birth control pills, injections and patches), thiazides (for high blood pressure or excessive fluid retention), corticosteroids, sympathomimetics (for example salbutamol used to treat asthma or pseudoephedrine for colds), danazol (medicine acting on ovulation), or thyroid replacement therapy.

Insulin requirements may also be affected by diphenylhydantoin (used to treat epilepsy). Insulin requirements may be decreased in the presence of agents such as oral medicines for the treatment of diabetes, salicylates (Aspirin*), sulfa antibiotics, certain antidepressants (monoamine oxidase inhibitors), beta- blockers, alcohol, ACE inhibitors and angiotensin II receptor blockers, and anabolic steroids.

Insulin requirements can be increased, decreased, or unchanged in patients receiving diuretics.

IMPORTANT:

PLEASE READ HUMULIN Product Monograph Page 27 of 54 The use of thiazolidinediones (such as rosiglitazone and pioglitazone), alone or in combination with other antidiabetic agents (including insulin), has been associated with heart failure and swelling of the lower extremities.

Please contact your physician immediately if you develop symptoms of shortness of breath, fatigue, exercise intolerance, or swelling of the lower extremities while you are on these agents. The presence of such diseases as acromegaly, Cushing’s syndrome, hyperthyroidism, and pheochromocytoma complicate the control of diabetes.

PROPER USE OF THIS MEDICATION INSTRUCTIONS FOR USE HUMULIN R cartridges are designed for use with Lilly injector systems (reusable pens). HUMULIN R cartridges and KwikPens (prefilled pens) are not designed to allow any other insulin to be mixed in the cartridge.

HUMULIN R cartridges and KwikPens MUST NOT be refilled and are not designed for use with a traditional syringe. Do not reuse needles. NEEDLES, CARTRIDGES, AND PENS MUST NOT BE SHARED with anyone including family members. Never share a HUMULIN KwikPen or cartridge, even if the needle on the delivery device is changed.

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HUMULIN (insulin, human biosynthetic) is contraindicated during episodes of hypoglycemia. HUMULIN is contraindicated in patients with hypersensitivity to human insulin or any of its excipients contained in the formulation (unless used as part of a desensitization program).

HUMULIN-N, HUMULIN MIXTURES, should not be given intravenously or used for treatment of diabetic coma. WARNINGS AND PRECAUTIONS General Serious Warnings and Precautions Hypoglycemia is the most common adverse effect of insulin products.

Glucose monitoring should be performed for all patients with diabetes mellitus treated with insulins. Uncorrected hypoglycemic or hyperglycemic reactions can cause loss of consciousness, coma or even death (see OVERDOSAGE, Symptoms and Treatment).

Any transfer of HUMULIN or HUMULIN MIXTURES should be made cautiously and only under medical supervision (see DOSAGE AND ADMINISTRATION). Fast-acting insulins should be combined with a longer-acting insulin or insulin infusion pump therapy to maintain adequate glucose control (see DOSAGE AND ADMINISTRATION).

HUMULIN and HUMULIN MIXTURES should not be mixed with any other insulin unless clearly indicated and done under medical supervision (see DOSAGE AND ADMINISTRATION). Under no circumstances should any HUMULIN MIXTURE be given intravenously.

Do not use the HUMULIN-N or HUMULIN MIXTURES if you see lumps that float or that stick to the sides of the vial, or if the contents of the vial are clear and remain clear after the bottle is shaken or rotated.

NOTE:

The contents of the vial or cartridge of HUMULIN-R should be clear. Do not use if cloudy. A few patients who experienced hypoglycemic reactions after being transferred to HUMULIN (insulin, human biosynthetic) have reported that these early warning symptoms were less pronounced than they were with animal-source insulin.

As with all insulin therapies, the duration of action of HUMULIN and HUMULIN MIXTURES may vary in different individuals or in the same individual according to dose, injection site, blood flow, temperature and level of physical activity.

HUMULIN Product Monograph Page 5 of 54 Hypokalemia is among the potential clinical adverse effects associated with the use of HUMULIN and all other insulin therapies. g. diarrhea). Stress or concomitant illness, especially infectious and febrile conditions may change insulin requirements.

In these instances, patients should contact their physician and carefully control their blood glucose (see Part III – Consumer Information). To avoid transmission of disease, a cartridge or prefilled syringe should not be used by more than one person.

The number and size of daily doses and the time of administration, as well as diet and exercise, are problems that require direct and continuous medical supervision. Usually, the most satisfactory injection time is before breakfast.

Insulin plus Thiazolidinediones (TZDs):

TZDs, alone or in combination with other antidiabetic agents (including insulin), can cause heart failure and edema. The combination of insulin with a TZD is not indicated for the treatment of type 2 diabetes mellitus. Please refer to the respective TZD product monograph Warnings and Precautions information when the use of these drugs in combination with any insulin, including HUMULIN R, HUMULIN N or HUMULIN 30/70, is contemplated.

Changes in Insulin Regimen / Transferring Patients from Other Insulins When patients are transferred between different types of insulin products, including animal insulins, the early warning symptoms of hypoglycemia may change or become less pronounced than those experienced with their previous insulin.

Transferring a patient to a new type or brand of insulin should be done only under strict medical supervision. , regular, NPH, or insulin analogs), or method of manufacture (recombinant DNA versus animal source insulin) may affect glycemic control and predispose to hypoglycemia or hyperglycemia.

Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of glucose monitoring. Changes in insulin dose or an adjustment in concomitant oral antidiabetic treatment may be needed. If an adjustment is needed, it may be done with the first doses or during the first few weeks or months and under medical supervision (see WARNINGS AND PRECAUTIONS).

Carcinogenesis and Mutagenesis Human insulin is produced by recombinant technology. No serious events have been reported in subchronic toxicology studies. Human insulin was not mutagenic in a battery of in vitro and in vivo genetic toxicity assays (see TOXICOLOGY).

HUMULIN Product Monograph Page 6 of 54 Endocrine and Metabolism Hypoglycemia Hypoglycemia is the most frequently occurring undesirable effect of insulin therapies, including HUMULIN. Severe hypoglycemia can result in temporary or permanent impairment of brain function and death (see ADVERSE REACTIONS).

Hypoglycemia may occur if the insulin dose is too high in relation to the insulin requirement (see OVERDOSAGE). Hypoglycemia can occur regardless of the type of insulin taken and may cause fatigue, sweating, heart palpitations, disturbed behaviour, hunger, convulsions or loss of consciousness.

In extreme circumstances, even death can occur without recognizable symptoms. , long duration of diabetes mellitus, diabetic nerve disease, intensified diabetes mellitus control, patients with psychiatric illness, elderly patients or use of medications such as beta blocking agents), the nature and intensity of early warning symptoms of hypoglycemia (pallor, sweating, anxiety, headache, tachycardia, hunger) may change or be less pronounced.

Hypoglycemic reactions following treatment with HUMULIN are mostly mild and easily managed. Changes in […]